This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. As the U.S. aging population increases, it is especially important to understand how ethanol affects older people. Aged females are at greater risk for the negative health consequences of ethanol consumption compared to aged males. Hormonal changes specific to aging females could contribute to changes in the effects of ethanol, which include greater sensitivity to certain subjective effects. This research will increase our understanding of the neuropharmacologic effects of ethanol in aged females and the role ovarian hormones. Positive modulation of the effects of the neurotransmitter gamma-aminobutyric acid (GABA) at GABA(A) receptors is a critical component of the pharmacologic effects of ethanol. Our studies will determine whether the neuropharmacologic mechanisms mediating ethanol effects 1) differ between young and aged female non-human primates, which have similar ethanol metabolism and reproductive hormone cyclicity as humans, and 2) are altered by surgically-induced menopause. The studies are using an operant procedure, drug discrimination, in which subjects are trained to press one lever after nasogastric administration of ethanol and another after water. Without taste cues, subjects must attend to the subjective or discriminative stimulus effects of ethanol. A food treat is delivered only after presses to the correct lever. After training, the subjects are tested for sensitivity to the discriminative stimulus effects of ethanol and the substitution of three progesterone derivatives produced by the ovaries that positively modulate GABA(A) receptors. These data will provide information about the role of ovarian hormones in age-related changes in sensitivity to ethanol and its neuropharmacologic mechanisms.